Finally, a mystery has been solved.
Nearly five months ago, a 30 year old woman named Jade Erick suffered a cardiac arrest, most likely due to anaphylactic shock, during the infusion of intravenous curcumin ordered by a California naturopath named Kim Kelly, ND (for Not-a-Doctor). Because Erick’s death was so sudden and dramatic, the story briefly made national news. I viewed the tragic incident as yet another example of why “licensed” naturopaths, such as those in California or other states that have made the mistake of passing laws allowing the licensing of naturopaths, are no less likely to mess up your health or even kill you than “unlicensed” naturopaths, such as the naturopath in Bowling Green who was shot by the husband of one of his patients. The reason for the shooting? That naturopath had told the man’s wife that “chemo is for losers” and treated her with the usual naturopathic voodoo, allowing the woman’s cancer to progress until it was no longer treatable with conventional medicine.
Jade Erick didn’t suffer from a life-threatening disease like cancer. She did, however, have a condition that almost certainly significantly affected her quality of life for the worse, namely eczema. Eczema is the name commonly given a group of medical conditions characterized by inflammation of the skin (i.e., rashes). The most common type of eczema is known as atopic dermatitis or atopic eczema, with the “atopic” referring to a group of diseases with an often inherited tendency to develop other allergic conditions. It’s a pretty common condition, too, with around 10% to 20% of infants being affected and around 3% of adults. Most children with eczema “outgrow” it, but some people continue to have symptoms on and off for the rest of their lives. Because eczema’s clinical course can be so varied and intermittent and also because the itching it causes can be very intense, it is a magnet for quacks like naturopaths. There are, of course, conventional medical treatments for eczema that relieve the itching and irritation and prevent rashes, but they leave much to be desired, again another characteristic of diseases or conditions that are quack magnets.
A little over a week ago, a number of readers sent me a link to an FDA safety alert and report of its investigation into Erick’s death and another case of a serious hypersensitivity reaction due to intravenous curcumin. Included with these two links was a link to an alert about the risk of compounding medications. It turns out that what likely killed Jade Erick was a hypersensitivity reaction to the use of a component that wasn’t pharmaceutical grade and is also known to cause hypersensitivity reactions. Let’s take a look.
Jade Erick and the naturopath who killed her
As I mentioned before, Jade Erick was an otherwise healthy 30 year old woman with a chronic medical condition. For whatever reason, however she found him, she sought out treatment from a naturopath named Kim Kelly, who, as it turns out, has been a vocal advocate of intravenous curcumin to treat…just about everything. Indeed, although after Erick’s death Kelly started scrubbing every mention of intravenous curcumin from his website, enough remained to demonstrate his enthusiasm for its use:
I am excited to announce that I’ve started administering intravenous curcumin. Curcumin has been used for thousands of years for culinary and medicinal reasons. People have used it to help with pain, inflammation, immune system, arthritis, liver conditions and cancer. It’s also been found that intravenous curcumin in combination with vitamin C and glutathione (I call it the “Mother of All Antioxidants”) has a potentiating effecting in helping people with chronic health conditions e.g. hepatitis C, liver fibrosis. Intravenous Curcumin is absorbed better, faster and can be given in much higher doses compared to taking it orally. Therefore, the benefits usually can be seen much sooner. Patients who have received it thus far have reported benefits very soon after treatment.
If you are suffering from any type of inflammatory condition, whether it be arthritis, autoimmune condition (e.g. scleroderma, lupus or rheumatoid arthritis), Alzheimers or dementia, this may be a great modality of treatment to try. It may require multiple treatments or may be just one treatment, depending on each person and the condition.
The safety, tolerability, and nontoxicity of curcumin at high doses have been well established by human clinical trials. Promising effects have been observed in patients with various pro-inflammatory diseases.
I can’t help but note that that last statement is absolutely false. Yes, orally administered curcumin is generally pretty safe even up to 8 g per day. However, intravenous curcumin hasn’t been well studied, as I discovered when I started doing more PubMed searches (although I did find a bunch of articles in which investigators were trying to use curcumin nanoparticles, micelles, and the like to administer curcumin IV). This is naturopathic “reasoning,” such as it is: If a little is good, a boatload would be better. Finally, if real medical science is investigating a natural product for one indication and it shows a bit of promise, then to naturopaths it must be a wonder medicine that cures everything—and I do mean everything. Take a look at the list of conditions for which Kelly claims treatment efficacy of IV curcumin:
- Inflammatory Bowel Disease (Crohn’s and Ulcerative Colitis)
- Post-Operative Inflammation
- Irritable Bowel Syndrome
- H. pylori infection
- Type 2 Diabetes
- Diabetic Nephropathy
- Alcohol Intoxication
- Chronic bacterial prostatitis
- Arsenic Exposure
Oddly enough, eczema is not on the list. Obviously, “Dr.” Kelly expanded his list before treating Ms. Erick. In any case, it’s always a huge red flag when I see a long list of unrelated diseases and conditions treated by the same drug or treatment. I mean, chronic bacterial prostatitis and atherosclerosis and arsenic exposure? Seriously? In any event, although curcumin has been a favorite of naturopaths for a long time, intravenous curcumin is a relative newcomer on the quack scene. The foremost promoter and popularizer of infusing this compound directly into the veins instead of administering it orally is Paul Anderson, who, as we will see, was so concerned about this death that he issued a disingenuous defense of what Kelly did.
As for Kelly himself, as I like to say, he is everything that organized naturopathy says a good “naturopathic physician” should be. Just look at his profile on his website:
Dr. Kim D. Kelly graduated from Bastyr University in 2001 and is a licensed Naturopathic doctor in the state of California. Growing up on a farm in Northern Minnesota is where he first had experience in the healing power of nature. This was further fostered when reading about the numerous clinical trials using alternative therapies when he was getting his Master’s of Public Health (MPH in Epidemiology) at the University of Minnesota. After realizing the power and effectiveness of alternative therapies, his career goal as Epidemiologist changed to wanting to become a Naturopathic Doctor; thus, he enrolled at Bastyr University in Seattle, WA.
Upon graduation from Bastyr, he underwent a rigorous three year training program at a cutting edge clinic, where he was trained by a team of medical and naturopathic doctors (Nazanin Kimiai, ND, LAc; Dietrich Klinghardt, MD, PhD; David Musnick, MD, MPH). Through his experience at this integrative clinic, Dr. Kelly learned the art and science of progressive healing modalities for musculoskeletal pain, autoimmune conditions, chronic infections (parasites, Lyme, mold), environmental & heavy metal toxicities and general health issues.
Dr. Kelly’s four years as technical director and consultant with Sabre Sciences has given him a strong background on use of bio-identical hormones and neurotransmitters for issues e.g. menopausal and andropause symptoms, PMS, insomnia, anxiety or chronic fatigue. His specialties include adrenal fatigue, thyroid disorders, hormonal issues in men and women (menopause, andropause, PMS, etc.), musculoskeletal pain and heavy metal detoxification. A lot of his practice also involves a technique called Biopuncture to help with chronic pain, headaches, gastritis, IBS and other health issues (See Service List for more details). He currently has an office in Encinitas.
Dr. Kelly has lectured locally and nationally on topics e.g. hormone balance for men and women, heavy metal toxicity and what we can do, nutritional research on Autism, gastrointestinal issues and natural medicine in San Diego.
In the world of naturopathy, Bastyr is the equivalent of Harvard or Stanford. Of course, being the Harvard or Stanford of quack schools is not saying much. After all, Bastyr recently sent a cease-and-desist letter to Britt Hermes, a former naturopath who graduated from Bastyr but eventually came to the realization that naturopathy is pure quackery and has been unrelentingly critical of her former alma mater ever since. My point, of course, is that Kelly graduated from what groups like the American Association of Naturopathic Physicians (AANP) view as the crème de la crème of naturopathy schools and is fully licensed in the largest state in the country. Of course, I can’t help but note that in his bio asserting his pseudoprofessional bona fides, he can’t help but mention one of naturopaths’ favorite forms of quackery, “heavy metal detox.” I find that appropriate.
Perusing the rest of Kelly’s website, even without the benefit of the almighty Wayback Machine at Archive.org, which rescues web pages from the memory hole every day, I found plenty of quackery offered by his practice. For instance, he offers biopuncture, naturopathic detoxing, hormonal balance treatment, IV nutrition, and “wellness programs.” Biopuncture, I note, is an unholy combination of acupuncture and homeopathy so quacky that Dr. Oz promoted it. Kelly describes it thusly:
Biopuncture is a technique that combines neural therapy, trigger point therapy, prolotherapy and homotoxicology. It stimulates the body’s own healing mechanisms thus speeding up the process of injury recovery, natural rejuvenation/repair and also lowers pain and inflammation. The technique involves using pin-prick needles to inject miniature amounts of homeopathic remedies under the skin or into muscle encouraging the body to start healing and to help stimulate local blood circulation.
In other words, it’s some most excellently ridiculous woo, a witches’ brew of quackery, to go along with all the other nonsense in Kelly’s blog, such as (of course) more biopuncture and more “detoxification,” along with other quackery such as adrenal fatigue treatment, intravenous vitamin C, and a dangerous modality like intravenous peroxide for chronic infections. All of this costs only $150 per 30 minutes plus the cost of the therapy.
Not surprisingly, when a real medical emergency happened right in his own office, “Dr.” Kelly wasn’t prepared to deal with it. The result is described in the FDA report:
On March 10, 2017, the U.S. Food and Drug Administration received an adverse event report concerning a 30-year-old female patient who experienced cardiac arrest after IV administration of a curcumin emulsion product compounded by ImprimisRx. The patient reportedly had a history of allergies and was being treated for eczema by a naturopathic doctor. Within minutes of starting the infusion, the patient became pulseless and required CPR. The patient suffered anoxic (depleted oxygen) brain injury and subsequently died. An adverse reaction to infused curcumin solution was identified as a cause of death by the local authorities.
So what caused the hypersensitivity reaction that killed Jade Erick within minutes of the start of her infusion of IV curcumin? The FDA thinks it’s found the cause both of her death and of a similar hypersensitivity that nearly killed a 71 year old man who was being treated for thrombocytopenia (a low platelet count) at a holistic health center. Amazingly, that “holistic” health center appears to have actually had medications to deal with an acute anaphylactic reaction, which kept him alive long enough to get him to an emergency room. In fairness, Erick’s reaction appears to have been so fast that there might not have been time to administer diphenhydramine and epinephrine.
Beware compounding pharmacies that play fast and loose with ingredients
In response to the reports of Jade Erick’s sudden death, the FDA did what the FDA does very well. It investigated. It turns out that the intravenous curcumin emulsion used was manufactured by ImprimisRx Pharmaceuticals, a compounding pharmacy based in San Diego, California. There are, of course, legitimate compounding pharmacies, and such pharmacies serve a useful role in medicine, but there are also a lot of compounding pharmacies that cater to naturopaths, mixing up combinations of supplements, “natural” medications, and the like for that particular market. ImprimisRx appears to be one such pharmacy, manufacturing both legitimate FDA-approved drugs and compounds like its Curcumin Emulsion MDV and, of course, intravenous vitamin C. It also manufactures intravenous EDTA for chelation therapy.
The FDA collected samples from the IV bag used to dose Jade Erick and from the ImprimisRx curcumin emulsion vial used to prepare the IV bag. It also analyzed the samples of ImprimisRx’s curcumin emulsion product and identified the presence of certain contaminants and impurities. It found a number of rather interesting (and disturbing) things. First, the FDA noted that there wasn’t nearly as much curcumin in ImprimisRx’s curcumin emulsion product as claimed on the labeling. The solution in the IV bag contained only 2.34 μg/mL of curcuminoids, which is only around 1% of the curcumin concentration intended to be administered. It also found that the concentration in the emulsion vial contained only around 0.205 mg/mL of curcuminoids, which is less than 2% of the curcumin concentration represented on the label. One of the big problems with administering curcumin is that it undergoes rapid degradation at physiologic pH, and that might explain why the concentration of curcumin in the vial was so much lower than what was represented on the label. Of course, a good compounding pharmacy should know these issues and limitations and take steps to mitigate them. Clearly ImprimisRx did not. As a result, Kelly and all the naturopaths who thought they were giving their patients “high dose” curcumin were probably giving them less than what a patient would get by taking curcumin supplements orally.
More importantly and relevant to what caused Jade Erick’s death, the FDA found this:
FDA collected and analyzed samples of PEG 40 castor oil from the same lot of ImprimisRx curcumin emulsion product that was administered to the female patient. FDA identified 1.25% w/w DEG [diethylene glycol] in the PEG [polyethylene glycol] 40 castor oil. The label of the tested PEG 40 castor oil includes the warning “CAUTION: For manufacturing or laboratory use only.” The PEG 40 castor oil used by ImprimisRx was ungraded, and not, for example, pharmaceutical grade or food grade. Ungraded products are suitable for general industrial or research purposes and typically are not suitable for human consumption or therapeutic use. There is no U.S. Pharmacopeia (USP) monograph for PEG 40 castor oil.
The FDA notes that drugs, including FDA-approved products, containing polyethylene glycol castor oil have been “associated with severe and sometimes fatal hypersensitivity reactions and include warnings about these reactions in their labels.” One example IV paclitaxel containing Cremophor® EL (PEG 35 castor oil), which can cause severe hypersensitivity reactions in up to 20% of patients. That’s why patients receiving paclitaxel are premedicated with steroids, and it’s why a new formulation lacking the PEG 35 castor oil, Abraxane, is coming into wider usage. The FDA further noted:
Some of the other ingredients in ImprimisRx’s product, including curcumin, also have been associated with hypersensitivity reactions when administered intravenously. There are reports of contact allergies to a metabolite of curcumin, tetrahydrocurcumin, for instance. In addition, there is little to no toxicologic or clinical information available regarding the safety of IV curcumin, and evidence is lacking that curcumin is an effective therapy for eczema or thrombocytopenia. There are no FDA-approved curcumin for injection products.
The ungraded PEG 40 castor oil in ImprimisRx’s curcumin emulsion product may have contained components that resulted in the hypersensitivity reactions. Castor bean seeds and pollens are known to be associated with hypersensitivity reactions. Food grade castor oil is processed to remove the potentially allergenic castor bean constituents, but ungraded PEG 40 castor oil may not be allergen free. In addition to allergens, other potentially harmful contaminants and impurities could be present in the ungraded PEG 40 castor oil.
It was also noted that DEG is a central nervous system depressant, as well as a potent kidney and liver toxin that can cause kidney failure. It’s commonly used in industrial products like antifreeze and brake fluid.
The FDA concluded:
FDA’s investigation into the adverse events associated with ImprimisRx’s curcumin emulsion product for injection highlights some of the risks associated with compounded drugs, particularly those that use non-pharmaceutical grade components and ingredients lacking a USP monograph. The risks illustrated in this case include:
- the absence of a label warning about hypersensitivity reactions associated with the PEG 40 castor oil;
- the use of an ungraded inactive ingredient, i.e., PEG 40 castor oil, that is not suitable for human consumption or therapeutic use and may contain impurities such as DEG; and
- the IV administration of curcumin, despite the fact that its safety profile by this route of administration has not been established, nor has its effectiveness in treating eczema or thrombocytopenia.
So basically, it appears from the FDA report that a perfect storm of woo killed Jade Erick: A naturopath using an unproven treatment plus a compounding pharmacy cutting corners manufacturing its products using PEG 40 castor oil that wasn’t pharmaceutical grade and failing to place a warning label on its curcumin emulsion warning that components of the emulsion can cause hypersensitivity reactions. According to the FDA, ImprimisRx recalled its unexpired products containing the ungraded castor oil on June 23, 2017, which was over two months after the second hypersensitivity reaction (in the 71 year old man) was reported.
The danger of some compounding pharmacies
Another lapse in this case included that there was no prescription for the IV curcumin found. At least, the company told a media outlet that it did not have a prescription. Britt Hermes, in her discussion of the case, speculated based on her experience as a naturopath about how such a thing might have happened and how Kelly might have obtained the curcumin for Erick without a prescription:
Kelly may have used a vial of the curcumin emulsion that was obtained under a prescription for another one of his patients. My former naturopathic colleagues in Arizona at times purchased compounded products in bulk for a single patient to then be used for multiple patients. This stockpiling allowed naturopathic doctors to have compounded drugs on-hand, thereby expediting treatments for multiple patients using only one prescription. Or, Kelly may have obtained the curcumin emulsion from a physician or another naturopathic doctor who had product on hand for their own patients. The borrowing of medical supplies, including compounded substances, is a common practice in the naturopathic community. Either way, using a prescription of one patient for another patient is not permitted by the FDA.
Worse, this sort of occurrence can’t be said to have been entirely unexpected, given ImprimisRx’s previous run-in with the FDA. Last year, the FDA inspected ImprimisRx’s manufacturing facility in Pennsylvania and found a number of violations. These included failures to test:
- aqueous solutions and suspensions or encapsulated powders to determine if they meet specifications for the intended, labeled dose of active drug ingredient
- products intended for inhalation to verify that the particle size is correct
- inhalation products for microbial contamination
- products to determine appropriate expiration dates
The inspection also found that there were “no written procedures for production and process controls to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess,” which likely explains a lot about how the curcumin emulsion could have a potency of only 2% of what was claimed on the label, especially since the FDA found a number of other lapses indicating what can only be called a lack of concern for preventing bacterial contamination and assuring that what is in the product matches what the label says.
Compounding pharmacies can play an important role in medicine. For instance, special compounding might be required if a patient needs a medication to be made without a certain dye or inactive ingredient because of an allergy or needs a medication in liquid or suppository form that is not manufactured in such forms. Unfortunately, a lot of companies go beyond such needs, as the FDA noted in a recent article on compounding pharmacies:
“Some aspects of these firms’ operations appear more consistent with those of drug manufacturers than with those of traditional pharmacies,” says Bernstein. “Some firms make large amounts of drugs that appear to be copies of FDA-approved, commercially available drugs when it does not appear that there is a medical need for an individual patient to receive a compounded version of the drug.”
The FDA also expressed concerns about compounding pharmacies just this year, noting serious incidents linked with them. Most of these incidents have to do with contamination with microorganisms. For instance, in 2012, there was an outbreak of fungal meningitis linked to an injectable steroid medication manufactured by a compounding pharmacy. In 2011 and 2012, 33 eye surgery patients in seven states suffered a rare fungal infection of the eye linked to injectable drug products, resulting in partial to severe vision loss, while in 2011 repackaged injections of Avastin (bevacizumab) also caused serious eye infections in the Miami area. These latter two incidents resulted in serious vision loss in some patients. Some patients injected with the contaminated Avastin lost the remaining vision in the eye being treated.
It’s stories like this that make me laugh derisively any time I hear a politician complain about FDA “overreach.” In reality, the reason these sorts of incidents occur with a distressing regularity is because the FDA is underfunded and understaffed. It has a hard time overseeing pharmaceutical company manufacturing facilities adequately, much less compounding pharmacies, allowing compounding pharmacies like ImprimisRx to continue doing business. Indeed, look at Imprimis Pharmaceuticals’ (IMMY) statement regarding the FDA’s findings. Basically, the company is trying to shift the blame for Jade Erick’s death from its product to…well…anyone else.
Imprimis had no knowledge of the allergy histories of the subject patients.
So what? Imprimis manufactured a product with components known to cause acute hypersensitivity reactions, and there was no warning of this on the product label.
FDA testing of the IV bag from the 30 year-old patient revealed “no drugs or poisons including diethylene glycol [DEG] at a level greater than 0.1% by volume, were identified in the IV bag contents using GC-MS.” We believe that evidence thus far does not support the 30 year-old patient’s death being caused by PEG 40 Castor Oil or DEG.
WTF? 0.1% is a high concentration for “drugs or poisons.” Basically, it’s one part in a thousand. This is not something that strikes me as exonerating Imprimis. Quite the contrary. It suggests that the FDA was quite correct about Imprimis’ shoddy manufacturing if “drugs or poisons” other than what was supposed to be in the product were present at a concentration as high as 0.1% Again, WTF?
PEG Castor Oils are suitable excipients used in both compounding and the pharmaceutical industry and there are multiple examples of commercial injections that are FDA approved for which polyethoxylated castor oils are a component of, such as paclitaxel injection, teniposide injection, docetaxel injection, and cyclosporine injection.
This is true. However, these drugs also have warnings that they can cause hypersensitivity reactions. As I mentioned above, in the case of paclitaxel and docetaxel (both taxanes), patients are premedicated with steroids because the risk of hypersensitivity reactions due to the PEG castor oil excipient is so high.
Imprimis received written documentation from its FDA registered and inspected supplier as to the suitability of its PEG 40 Castor Oil material for use in human compounded products. This documentation, received prior to use of the material, stated specifically, “We certify that our product, P2404 PEG Castor Oil is manufactured, packaged and held in compliance with 21 CFR, Parts 210 and 211 of the United States Code of Federal Regulations and is suitable for pharmacy compounding use.”
OK, Imprimis and the FDA can’t both be correct. Imprimis denies using non-pharmaceutical grade PEG 40 Castor Oil, and the FDA found that it did. I would tend to go with the FDA on this. Basically, Imprimis is blaming its supplier, which, I suppose, is possible, but given all the other negative findings in the FDA inspection last year I’m not about to give Imprimis the benefit of the doubt about anything.
According to federal and state regulations, it is permissible for Imprimis (and any other pharmacy) to use curcumin in human drug compounding (FDA’s 503A Category 1 for Bulk Drugs for Use in Compounding).
I note that this statement, dated July 1, lists curcumin as being nominated for use in compounding under section 503A and lists it among other substances being under evaluation. Seriously, Imprimis, did you really think we wouldn’t click on the link and read the actual FDA document?
Imprimis maintains that the prescriptions it filled for the subject curcumin emulsion vials were valid, labeled properly, and that the curcumin emulsion dispensed was correctly made according to state and federal law.
Given that intravenous curcumin is not FDA-approved for any indication, I find this hard to believe. If true, though, it is a huge glaring problem with the law that sleazy companies like Imprimis exploit.
The Great Yellow Hope diminished
It’s not surprising that naturopaths would be attracted to curcumin as the cure for everything. They love to latch on to natural compounds that show promise in clinical medicine, and it is true that curcumin has been studied widely as a potential cancer treatment, so much so that I used to jokingly refer to it as the “Great Yellow Hope” for cancer. It’s also been studied for inflammatory diseases as well. Indeed, there have been lots of seemingly promising experiments in vitro and in animals published, but clinical trials carried out thus far have been very disappointing. A recent review in the Journal of Medicinal Chemistry was particularly damning:
Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double- blinded, placebo controlled clinical trial of curcumin has been successful.
I explained, with the help of Derek Lowe, what PAINS and IMPS compounds are, why curcumin is almost certainly one of these, and further why that means curcumin’s benefits likely will not translate into clinical practice.
Here’s a general rule of thumb, particularly with a compound like curcumin. When clinical studies are this unimpressive and everyone’s scrambling to handwave “alternative explanations” for efficacy, it’s not a good sign. Indeed, the enthusiasm for curcumin among cancer researchers has always puzzled me, given how weak the existing evidence base is for its efficacy and the serious drawbacks it has in terms of solubility, instability, and bioavailability. Naturopaths, as is their wont when looking for legitimacy, take that enthusiasm and turn it up to 11, because the success and adoption of curcumin by conventional medicine would validate their worldview about the usefulness of natural products. It is this worldview that leads to tragedies like the death of Jade Erick.
Unfortunately, it appears that naturopaths will never learn. After the death of Jade Erick, naturopaths did what naturopaths always do after one of their own causes harm to a patient through quackery. They circled the wagons and tried to find strategies not to have to take serious disciplinary action against Kelly Kim.
There is, however, a very interesting wrinkle. The California law providing for naturopathic licensure is scheduled to sunset at the end of this year. There is, however, a new bill (SB 796), introduced by Jerry Hill (D-San Mateo) that would extend naturopathic licensure to 2022. The case of Jade Erick would thus seem to represent a dire threat to naturopathic licensure in California. “Seem” is the operative word, sadly. The bill passed the California Senate unanimously in July and appears to be wending its way through the Assembly committee process unimpeded.
Between the government-imposed weakness of the FDA mandated by anti-regulation politicians and the willingness of politicians to keep licensing quackery, I fear there will be more cases like Jade Erick.